Phosphorylation signals are conserved in eukaryotes and play an important role in various physiological processes. Among those, abnormal phosphorylation of tyrosine residues is known to play a key role in the onset of many hereditary and acquired diseases. Currently, therefore, many tyrosine kinase inhibitors are clinically applied.
On the other hand, dephosphorylation enzyme termed phosphatases inactivates a phosphorylation signal pathway by dephosphorylating a certain site in the pathway. Among the dephosphorylation enzymes, tyrosine dephosphorylation enzymes have been being elucidated to function specifically and initiatively in the regulation of various physiological processes (see Non-Patent Documents 1-3). For example, 14 tyrosine dephosphorylation enzymes have been so far identified as a responsible gene for an autoimmune disease, diabetes, hereditary disease, and muscular disease. In addition, there are at least 30 known tyrosine dephosphorylation enzymes associated with the onset of cancer (see Non-Patent Document 4). Currently, however, since their physiological roles and target pathways are not elucidated, development of clinically applicable tyrosine dephosphorylation enzyme inhibitors has not been advanced well yet (see Non-Patent Document 5).
The present inventors have identified or cloned two dual specificity phosphatases (DSPs), which are a kind of tyrosine dephosphorylation enzyme, from human cells by using degenerate polymerase chain reaction (PCR) and expression sequence tag (EST) data search (GenBank accession No. AB103375; GenBank accession No. AB103376). These DSPs are now known as DUSP13 and DUSP26, respectively. For DUSP13, mouse homologue TMDP (testis- and skeletal muscle-specific DSP) is known. TMDP expression is specific to testis and skeletal muscle in mouse. Mouse TMDP is pointed out to be involved in spermatogenesis (see Non-Patent Document 6).
However, it remains to be known about physiological roles of human DUSP13 and DUSP26. Furthermore, there has been no report on a tyrosine dephosphorylation enzyme with regard to its physiological roles in heart and its relation to heart diseases.    [Non-Patent Document 1] Hunter T (1989) Cell. 58: 1013-1016    [Non-Patent Document 2] Mustelin T (2002) Curr Dir Autoimmun. 5: 176-190    [Non-Patent Document 3] Mustelin T et. al. (2002) Front Biosci. 7: 918-969    [Non-Patent Document 4] Andersen J N et. al. (2004) FASEB J. 18: 8-30    [Non-Patent Document 5] Alonso A et. al. (2004) Cell. 117: 699-711    [Non-Patent Document 6] Biochem. J. (1999) 344: 819-825